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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2840-2848. Prepublished online as a Blood First Edition Paper on July 6, 2004; DOI 10.1182/blood-2004-03-0859. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0859v1 104/9/2840    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Grossman, W. J. Articles by Ley, T. J. Search for Related Content PubMed PubMed Citation Articles by Grossman, W. J. Articles by Ley, T. J. Related Collections Immunobiology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells William J. Grossman, James W. Verbsky, Benjamin L. Tollefsen, Claudia Kemper, John P. Atkinson, and Timothy J. Ley From the Department of Pediatrics, Division of Hematology/Oncology and the Division of Rheumatology, St Louis Children's Hospital, St Louis, MO; and the Department of Internal Medicine, Siteman Cancer Center and the Division of Rheumatology, Washington University School of Medicine, St Louis, MO. Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the perforin/granzyme pathway as a major mechanism to kill pathogen-containing cells and tumor cells.1,2 Dysregulation of this pathway results in several human diseases, such as hemophagocytic lymphohistiocytosis. Here we characterize the single-cell expression pattern of granzymes A and B in human lymphocytes using a flow cytometry-based assay. We demonstrate that most circulating CD56+8- NK cells, and approximately half of circulating CD8+ T lymphocytes, coexpressed both granzymes A and B. In contrast, few circulating CD4+ T lymphocytes expressed granzymes A or B. Activation of CD8+ T lymphocytes with concanavalin A (ConA)/interleukin-2 (IL-2), and activation of CD4+ T lymphocytes with antibodies to CD3/CD28 or CD3/CD46 (to generate T regulatory [Tr1] cells), induced substantial expression of granzyme B, but not granzyme A. Naive CD4+CD45RA+ cells stimulated with antibodies to CD3/CD46 strongly expressed granzyme B, while CD3/CD28 stimulation was ineffective. Finally, we show that granzyme B-expressing CD4+ Tr1 cells are capable of killing target cells in a perforin-dependent, but major histocompatibility complex (MHC)/T-cell receptor (TCR)-independent, manner. Our results demonstrate discordant expression of granzymes A and B in human lymphocyte subsets and T regulatory cells, which suggests that different granzymes may play unique roles in immune system responses and regulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Serafini, M. Andreani, M. Testi, M. Battarra, A. Bontadini, E. Biral, K. Fleischhauer, S. Marktel, G. Lucarelli, M. G. Roncarolo, et al. Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia Haematologica, October 1, 2009; 94(10): 1415 - 1426. [Abstract] [Full Text] [PDF] J. L. Meade, E. B. Wilson, T. D. Holmes, E. A. de Wynter, P. Brett, L. Straszynski, P. A. S. Ballard, J. A. Trapani, M. F. McDermott, and G. P. Cook Proteolytic Activation of the Cytotoxic Phenotype during Human NK Cell Development J. 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